Biological systems have long recognized the importance of macromolecular diversity and have evolved efficient processes for the rapid synthesis of sequence-defined biopolymers. However, achieving sequence-control via synthetic methods has proven to be a difficult challenge.
Spatial control of monomer sequence along a polymer backbone is essential to the complex self-assembly of proteins and nucleic acids. To achieve macromolecular diversity, biological systems have evolved extremely efficient processes for the rapid synthesis of sequence-defined biopolymers virtually error free. Similarly, achieving primary sequence control using synthetic monomers should facilitate control over structural properties such as folding, self-assembly into nanostructures, structural stimuli response and formation of catalytic sites. These structural properties will invariably determine bulk material properties including solubility, conductivity, elasticity, non-fouling, biocompatibility, and catalytic performance. Understanding sequence-structure-material property relationships is of paramount importance towards our ability to carry out predictive bottom-up materials design and fabrication. Progress towards this goal requires the development of reliable methods for achieving precise polymeric sequence-control. However, current approaches to sequence-control are plagued by long assembly times and low yields due to the tedious protection and deprotection steps required for iterative sequence-controlled monomer ligation